Apelin Gene Therapy Increases Autophagy Via Activation of Sirtuin 3 in Diabetic Heart
Long known to augment the risk for cardiovascular disease, Diabetes Mellitus
increases mortality of patients with Heart Failure over that observed in HF patients without
DM. Cardiovascular disease is one of the major complications of DM.
Clinical studies show that Myocardial Infarction is the leading cause of morbidity
and mortality in the patients with DM. A population-based study also reveals that the incidence
of MI in diabetic patients is significantly higher than non-diabetic patients.
Therefore, it is urgent to develop new agents for the treatment of post-MI heart failure in DM.
Apelin is a bio-activated peptide which binding to the apelin receptor.
Apelin has been shown to protect the heart against ischemia injury and reduce infarct size.
A recent study also showed that deficiency of apelin exacerbated ischemia-reperfusion injury.
We have reported that over expression of apelin promoted myocardial angiogenesis and
improved cardiac function in post-MI diabetic STZ mice and these beneficial effects of apelin
were mediated through activation of Sirt.
Sirt is a member of a highly conserved family of protein deacetylases, which is closely
associated with the prolonged lifespan of human.10 Sirt3 has been shown to regulate cardiomyocyte
apoptosis, survival and cardiac hypertrophy.
Previously, we also observed that treatment with Bone Marrow Cells over-expressing apelin
enhanced myocardial angiogenesis and functional recovery, accompanied by increased
Sirt3 levels in the ischemic heart. Our study further showed that knockout of Sirt3 blunted
the protective effect of apelin in cultured EPCs.
Diabetes Res Open J. 2015; 1(4): 84-91. doi: 10.17140/DROJ-1-115
